The Department of Biochemistry at Rush-Presbyterian-St. Luke's Medical Center arose as a result of a merger between clinical chemistry laboratories of St. Luke's and Presbyterian Hospitals in 1956. Initially, its mission was to provide clinical chemistry services for the newly established Presbyterian-St. Luke's Hospital on the West side of Chicago. Eventually, however, as the relationship between the Hospital and the nearby University of Illinois College of Medicine developed in the realm of clinical training of medical students and other endeavors, research became a major responsibility of the Department as well. Reflecting such a dual mission and upon a recommendation by Dr. R.J. Winzler, head of the Department of Biochemistry at University of Illinois, Dr. Max Rafelson was appointed to the Hospital's Department of Biochemistry chairmanship in 1961. he was an accomplished clinical biochemist as well as a research in the area of amino acid metabolism and serum glycoprotein chemistry. Dr. Rafelson proceeded to hire several research-oriented biochemists, who were also appointed to the faculty of University of Illinois Department of Biochemistry. As such, these individuals were assigned duties as teachers at the University and were able to attract its graduate students, who did their dissertation research in the Department's laboratories.

In the early 1970's, following a merger between Presbyterian-St.Luke's Hospital and the then inactive Rush Medical College, Dr. Rafelson was elevated to a deanship position and Dr. Howard Sky-Peck, a cancer researcher, was chosen to lead the Department of Biochemistry. The newly activated Rush Medical College appointed members of the Department to its faculty, and the Department thus acquired a third major responsibility, i.e., teaching of medical students and, after formation of the Rush University, students in other medically-related professions. Faculty appointments at the University of Illinois, and therefore the training of its graduate students, continued to be maintained.

In 1980, after the resignation of Dr. Sky-Peck as the Department's chair, Dr. Klaus Kuettner, a distinguished researcher in the area of connective tissue biochemistry, assumed leadership role in the Department. His 20+ year tenure as the Department's chair was characterized by a rapid expansion of its faculty and laboratory space, high degree of research productivity, and recognition of the Department throughout the world as a center of excellence in connective tissue research. Extensive cooperation between the Department on the one hand, and the clinical Departments of Orthopedic Surgery and Rheumatology on the other, the establishment of its own Ph.D. program in 1982, and a collaborative research effort on part of the Department's faculty in the area of cartilage biochemistry and its degenerative disease called osteoarthritis contributed in no small way to the success of the Department. The Department is especially proud of its graduate program, which has so far produced some 50 doctoral-level professionals. Following the retirement of Dr. Kuettner as the Department's chair in 2002, Dr. Ted Oegema, a connective tissue researcher from the University of Minnesota, was selected to lead the Department, and all indications are that under his mentorship, the Department will continue to occupy a leadership position in teaching and research among the world's medical schools.